Intervention Protocol Template

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Protocol TEMPLATE: Intervention Study (Clinical Trials)

This template can be modified to accommodate a variety of intervention study designs. Sections that are not applicable can be deleted. Delete the sections in blue or red and save the final document with all “track changes” accepted before submission.

Additional information for using this templatewith examples for each section is available the IRB intranet site at: The investigator is strongly advised to review this information before writing his/her protocol.

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Table of Contents

Table of Contents

Abbreviations and Definitions of Terms

Abstract

Protocol Synopsis

EXAMPLE: Table 1: Schedule of Study Procedures

EXAMPLE: Figure 1: Study Diagram

1Background Information and Rationale

1.1Introduction

1.2Name and Description of Investigational Product or Intervention

1.3Findings from Non-Clinical and Clinical Studies

1.3.1Non-Clinical Studies

1.3.2Clinical Studies

1.4Selection of Drugs and Dosages

1.5Relevant Literature and Data

1.6Compliance Statement

2Study Objectives

2.1Primary Objective (or Aim)

2.2Secondary Objectives (or Aim)

3Investigational plan

3.1General Schema of Study Design

3.1.1Screening Phase

3.1.2Study Treatment Phase (start of the study intervention)

3.1.3Phase 2 (Use an appropriate descriptor such as “Open-label Treatment” )

3.1.4Follow-up Phase

3.2Allocation to Treatment Groups and Blinding

3.3Study Duration, Enrollment and Number of Sites

3.3.1Duration of Study Participation

3.3.2Total Number of Study Sites/Total Number of Subjects Projected

3.4Study Population

3.4.1Inclusion Criteria

3.4.2Exclusion Criteria

4Study Procedures

4.1Screening Visit

4.2Study Treatment Phase

4.2.1Visit 1

4.2.2Visit 2

4.2.3Visit 3

4.3Phase 2 of the Study (e.g. Open-Label Treatment)

4.3.1Visit 4

4.3.2Visit 5

4.4Follow-up Phase (only if applicable)

4.4.1Visit 6

4.4.2Visit 6: End of Study

4.5Unscheduled Visits

4.6Concomitant Medication

4.7Rescue Medication Administration

4.8Subject Completion/Withdrawal

4.8.1Early Termination Study Visit

5Study Evaluations and Measurements

5.1Screening and Monitoring Evaluations and Measurements

5.1.1Medical Record Review

5.1.2Physical Examination

5.1.3Vital Signs

5.1.4Laboratory Evaluations

5.1.5Other Evaluations, Measures

5.2Efficacy Evaluations

5.2.1Diagnostic Tests, Scales, Measures, etc.

5.3Pharmacokinetic Evaluation

5.4Safety Evaluation

6STATISTICAL CONSIDERATIONS

6.1Primary Endpoint

6.2Secondary Endpoints

6.3Statistical Methods

6.3.1Baseline Data

6.3.2Efficacy Analysis

6.3.3Pharmacokinetic Analysis

6.3.4Safety Analysis

6.4Sample Size and Power

6.5Interim Analysis

7Study Medication (Study DEVICE or OTher Study INTERVENTION)

7.1Description

7.1.1Packaging

7.1.2Labeling

7.1.3Dosing

7.1.4Treatment Compliance and Adherence

7.1.5Drug Accountability

8SAFETY MANAGEMENT

8.1Clinical Adverse Events

8.2Adverse Event Reporting

8.3Definition of an Adverse Event

8.4Definition of a Serious Adverse Event (SAE)

8.4.1Relationship of SAE to study drug or other intervention

8.5IRB/IEC Notification of SAEs and Other Unanticipated Problems

8.5.1Follow-up report

8.6Investigator Reporting of a Serious Adverse Event to Sponsor

8.7Medical Emergencies

9STUDY ADMINISTRATION

9.1Treatment Assignment Methods

9.1.1Randomization

9.1.2Blinding

9.1.3Unblinding

9.2Data Collection and Management

9.3Confidentiality

9.4Regulatory and Ethical Considerations

9.4.1Data and Safety Monitoring Plan

9.4.2Risk Assessment

9.4.3Potential Benefits of Trial Participation

9.4.4Risk-Benefit Assessment

9.5Recruitment Strategy

9.6Informed Consent/Assent and HIPAA Authorization

9.6.1Waiver of Consent

9.6.2Waiver of Assent

9.6.3Waiver of HIPAA Authorization

9.7Payment to Subjects/Families

9.7.1Reimbursement for travel, parking and meals

9.7.2Payments to parent for time and inconvenience (i.e. compensation)

9.7.3Payments to subject for time, effort and inconvenience (i.e. compensation)

9.7.4Gifts

10PUBLICATION

11References

Appendix

Be sure to update the Index after the protocol is finalized. In MS Word, update using the INSERT menu, Index and Tables.

Abbreviations and Definitions of Terms

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Abstract

Use JAMA format ( Limit to 150 – 200 word abstract, written for lay members. This abstract is used in the IRB database and in the minutes of meetings.

Context: (Background)

Include 1 - 3 sentences about the clinical importance of the condition and the importance of the research question.

Objectives: (primary and important secondary objectives)

State the precise objective or study question

If more than 1 objective, limit to only the key secondary objectives.

Study Design:

Basic design: Randomized controlled trial, cohort study, case-control study, cross-sectional study, etc.

Setting/Participants:

The setting including location (referral or community center) and level of care (inpatient or outpatient)

The number of sites,

The number and description of participants including key eligibility criteria

Study Interventions and Measures:

Study drug, or other intervention and main monitoring procedures

Main study outcome measures (assessments of primary and key secondary endpoints)

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Protocol Synopsis

(Do NOT include a Synopsis if submitting protocol for expedited review)

• To determine (obtain, evaluate, verify, etc.) …

• To determine (obtain, evaluate, verify, etc.) …
• Etc.

1. Subjects age X – X
2. Include main criteria but does not need to be complete, etc.

1. Subjects with X or Y, etc.

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EXAMPLE: Table 1: Schedule of Study Procedures

This table is an example of a schedule of procedures. The Investigator should construct a table based on the procedures in the protocol. If the study involves more than 1 or 2 visits, it is often preferable to include this table as an Appendix to the Consent Form. This simplifies the consent form.

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EXAMPLE: Figure 1: Study Diagram

A flow diagram of the study may be relevant to explain the flow of subjects in the trial. An example flow diagram for randomized, controlled clinical trial design is included as an example below.

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1Background Information and Rationale

Section 1 should be no more than 3 – 5 pages. Refer the reader to the applicable grant, or attached literature references for more detailed information. If referring to the grant it is helpful to include page citations.

1.1Introduction

Brief paragraph or two to describe the setting and rationale for the study. The details of the background go into Section 1.6

1.2Name and Description of Investigational Product or Intervention

Name and description of the study intervention (drug, device, diagnostic, diet, experimental psychological therapy, etc.). If a drug, device or biologic, the specific description, packaging, control systems will go in Section 7.

1.3Findings from Non-Clinical and Clinical Studies

(This section is only applicable for drugs, biologics and devices)

1.3.1Non-Clinical Studies

1.3.2Clinical Studies

1.3.2.1Human Pharmacokinetics

1.3.2.2Clinical Studies in Adults

1.3.2.3Clinical Studies in Children

1.4Selection of Drugs and Dosages

Description of dosage forms available and those to be used in study

1.5Relevant Literature and Data

Overview of the literature and data relevant to the trial and provide background for the trial. Also the relevant literature establishing the validity for scales, evaluation tools etc. The reference citations should be listed at the end in Section 11. It is usual to limit this to 10 (at most 20) key references.

1.6Compliance Statement

This study will be conducted in full accordance all applicable Children’s Hospital of Philadelphia Research Policies and Procedures and all applicable Federal and state laws and regulations including 45 CFR 46, 21 CFR Parts 50, 54, 56, 312, 314 and 812 and the Good Clinical Practice: Consolidated Guideline approved by the International Conference on Harmonisation (ICH). Note: Only include the sections of Title 21 if the study is regulated by the FDA. Only include ICH compliance if the study will actually comply with these requirements.All episodes of noncompliance will be documented.

The investigators will perform the study in accordance with this protocol, will obtain consent and assent, and will report unanticipated problems involving risks to subjects or others in accordance with The Children’s Hospital of Philadelphia IRB Policies and Procedures and all federal requirements. Collection, recording, and reporting of data will be accurate and will ensure the privacy, health, and welfare of research subjects during and after the study.

2Study Objectives

State the overall objectives of the study.

The purpose of the study is to determine the (efficacy, pharmacokinetics, safety etc.) of ….

2.1Primary Objective (or Aim)

The primary objective of this study is to determine the whether the XXX (intervention) reduces, increases, etc. outcome measure XXX in children X to X years. This should be specific, for example: “to determine if enalapril decreases systolic blood pressure after 4 weeks compared to placebo.”

The primary objective should be both the most important and the objective on which the study sample size is based. Objectives (aims) are usually phrased in some variant of “…to determine…”. Protocols differ from grants in that they do not usually enumerate specific hypotheses. If included, these belong in the Analysis section.

2.2Secondary Objectives (or Aim)

The secondary objectives are to:

• Determine if there is a relationship between X to Y.
• Determine the pharmacokinetics of drug X.
• Evaluate the tolerability and safety of XXXX for short-term administration in the stated population.
• Etc.

3Investigational plan

3.1General Schema of Study Design

Section 3 is a brief overview of the study design. In Sections 3.1.1 – 3.1.4 include brief overview of the study phases (Screening, Baseline assessment, Treatment Phase, Follow-Up, etc.).

Section 3.1 is intended to be a brief overview. Do not put the details of the entire study into this Section. Section 4 is where the details of the study and its procedures belong. A description of the study design should be included, e.g., randomized controlled trial, concurrent or non-concurrent (retrospective) cohort study, case-control study, cross sectional study, pharmocokinetic-pharmacodynamic study, descriptive study, natural history study, evaluation of a diagnostic, etc. Provide a general description here and a general description of the various phases in Sections 3.1.1, 3.1.2, etc.

Reference to Figure of Study Schema and to Table of Procedures as applicable.

3.1.1Screening Phase

How will subjects be identified, screened and how will they be approached for informed consent and subject assent.

For example, “Potential subjects will be screened using the protocol inclusion and exclusion criteria. Subjects will be recruited into two strata: children 6-12 years of age, and children 13-16 years of age with a goal of 50% of subjects per age strata.

Parental/guardian permission (informed consent) and, if applicable, child assent, will be obtained prior to any study related procedures being performed, including discontinuation of current therapy. Blood samples will be drawn to confirm eligibility based on clinical laboratory parameters. Females  11 years of age will have a urine pregnancy test.”

3.1.2Study Treatment Phase (start of the study intervention)

Description of Phase 1 of the study.

3.1.3Phase 2 (Use an appropriate descriptor such as “Open-label Treatment” )

(If applicable) Description of Phase 2 of the study.

3.1.4Follow-up Phase

(If applicable) To be eligible for the follow-up phase, subjects must either have (1) ……

The follow-up phase will continue for up to XXXX days.

3.2Allocation to Treatment Groups and Blinding

Describe the method for treatment allocation. If the study is randomized provide an overview of the process - who will generate the randomization sequence, how will the sequence be generated (table of random numbers, computer, etc.), where will the schedule be maintained, how will the assignment be concealed from the investigators. If there will be stratification, describe the groups. If blocking will be used, do NOT include the block size(s). Describe how blinding (if any) will be maintained.

3.3Study Duration, Enrollment and Number of Sites

3.3.1Duration of Study Participation

This section refers to the duration of the subject’s participation, not the duration of the study. The study duration per subject will be up to XXX days, with up to XXX days screening, up to XXX days Phase 1, up to XXX days Phase 2, and XXX days follow-up.

3.3.2Total Number of Study Sites/Total Number of Subjects Projected

The study will be conducted at approximately XX investigative sites in the United States and XXXX.

Recruitment will stop when approximately XXX subjects are ….. It is expected that approximately XXX subjects will be enrolled to produce XXXX evaluable subjects.

3.4Study Population

The study population for every type of study design is defined by Inclusion and Exclusion criteria. A few examples are included below.

3.4.1Inclusion Criteria

1)Males or females age X to XX years.

2)Weight  XX kg.

3)Girls  11 years of age must have a negative urine/serum pregnancy test and must use an acceptable method of contraception, including abstinence, a barrier method (diaphragm or condom), Depo-Provera, or an oral contraceptive, for the duration of the study.

4)Additional criteria as required

5)Parental/guardian permission (informed consent) and if appropriate, child assent.

3.4.2Exclusion Criteria

1)Exclusion 1

2)Exclusion 2

3)Laboratory abnormalities that indicate clinically significant hematologic, hepatobiliary, or renal disease (EXAMPLE below):

AST/SGOT> 2.0 times the upper limit of normal

ALT/SGPT> 2.0 times the upper limit of normal

Total bilirubin> 2.0 times the upper limit of normal

Hemoglobin < 9 gm/dL

White blood cell count< 3,000/ mm3

Platelet count< 100,000/mm3

4)Any investigational drug use within 30 days prior to enrollment.

5)Pregnant or lactating females.

6)Parents/guardians or subjects who, in the opinion of the Investigator, may be non-compliant with study schedules or procedures.

Subjects that do not meet all of the enrollment criteria may not be enrolled. Any violations of these criteria must be reported in accordance with IRB Policies and Procedures.

4Study Procedures

This section should list the procedures, observations, measures, etc. at each study visit, including history, examination, study drug administration or other interventions. Section 4 lists what will be done. Section 5 describes how it will be done. For complicated studies with several visits, it is recommended that the investigator create a Table of Procedures (page x).

4.1Screening Visit

List the timing and all of the procedures to be performed at the screening visit. This can be a simple bullet list.

• Informed Consent
• Physical Exam
• Vital Signs
• Laboratory tests
• Medical Record Review

4.2Study Treatment Phase

General overview of this phase.

4.2.1Visit 1

Detailed description of study visit including all procedures. This is usually included as a simple bullet list of all of the interventions, monitoring procedures and measurements that will take place. The study coordinator should be able to quickly review the list of procedures at each visit in order to correctly execute the study.

• Physical Exam
• Vital Signs
• Laboratory tests
• Start study intervention
• Dispense study diary
• Medical Record Review

4.2.2Visit 2

Detailed description of study visit including all procedures.

• Physical Exam
• Vital Signs
• Laboratory tests
• Collect unused study drug
• Dispense study drug
• Assess possible adverse events
• Medical Record Review

4.2.3Visit 3

• Etc…

4.3Phase 2 of the Study (e.g. Open-Label Treatment)

(Only include if applicable) General description of the phase.

4.3.1Visit 4

Detailed description of study visit including all procedures – listed like above examples.

4.3.2Visit 5

Detailed description of study visit – listed like above examples.

4.4Follow-up Phase (only if applicable)

General overview of this phase.

4.4.1Visit 6

Detailed description of study visit including all procedures – listed like above examples.

4.4.2Visit 6: End of Study

Detailed description of study visit including all procedures – listed like above examples.

4.5Unscheduled Visits

Description of how unscheduled visits will be handled.

4.6Concomitant Medication

(Include if appropriate)Example: All prior and concomitant medications used within XX days prior to the screening visit and through the end of the study will be recorded. The dates of administration, dosage, and reason for use will be included.

4.7Rescue Medication Administration

If subjects may receive rescue medication for adverse reactions or inadequate response to study medication, the options and how the decision will be made to permit such treatment should be included here.

4.8Subject Completion/Withdrawal

Criteria for withdrawal of subjects and plans for provision of care after withdrawal. Example: Subjects may withdraw from the study at any time without prejudice to their care. They may also be discontinued from the study at the discretion of the Investigator for lack of adherence to study treatment or visit schedules, AEs, or due to REASON (list). The Investigator or the Sponsor (if applicable) may also withdraw subjects who violate the study plan, or to protect the subject for reasons of safety or for administrative reasons. It will be documented whether or not each subject completes the clinical study. If the Investigator becomes aware of any serious, related adverse events after the subject completes or withdraws from the study, they will be recorded in the source documents and on the CRF.